Triethylamine → 3-(4-(2-isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole

HRID 924197Notes

Reaction equation

HRID 924197 reaction equation
[CH3:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[CH:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[N:14]=2)=[CH:9][CH:8]=1)C(O)=O.C([N:31]([CH2:34]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:37]C1C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[N:31]([CH:2]([CH3:1])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:17]=[CH:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]([O:24][C:25]([F:26])([F:27])[F:28])=[CH:22][CH:23]=3)[N:14]=2)=[CH:11][CH:12]=1)=[C:34]=[O:37]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 904041342-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-propanoic acid

Product 1

HCID 904040983-(4-(2-isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-propanoic acid (0.84 g, 2.2 mmol) in toluene (21.6 mL) was added triethylamine (0.33 mL, 2.4 mmol) and diphenyl phosphorazidate (0.47 mL, 2.2 mmol) and the solution was stirred at room temperature for 2 hours. The reaction was diluted with ethyl acetate and water and the layers separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was loaded onto a Celite® cartridge and purified by flash column chromatography using 0-100% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent to afford the title compound as a white solid (0.53 g, 58%): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.21-8.11 (m, 2H), 7.88-7.77 (m, 2H), 7.39 (d, J=8.3 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 3.94-3.80 (m, 1H), 2.87 (d, J=6.8 Hz, 2H), 1.35 (d, J=6.5 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 389 ([M+H]+).

Workup

  1. customthe layers separated
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-2d53cb496e1e4a8994ec1e07f36e1c85
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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